Silver has been long recognized for its antimicrobial properties. It was shown in the late 19th century that the ionic state of silver was the only form of silver that possessed this property (Ravelin, J. Sci. Nat. Vol. 11, p 93-102, 1869). It was subsequently shown that only minute amounts of silver are needed to demonstrate the antimicrobial effect (van Naegeli, V., Deut. Schr. Schweiz. Naturforsch. Ges., Vol. 33, p 174-182, 1893). The predominant forms of silver are in one of two oxidation states. The reduced form of silver is the metallic form commonly found in ornaments and jewelry. This form possesses no antimicrobial properties. The other common form is the oxidized ionic state also known as Ag+ which is the antimicrobial form of silver. Ag+ as the free ion is unstable and is almost always found in a complex with negatively charged elements or compounds. Ionic silver bound to these negatively charged groups often disrupts normal function and is commonly cited as the explanation of the mode of action of silver (Hugo, W. B. and A. D. Russell, Prog. Med. Chem., Vol. 31, p 351-368, 1994). These negatively charged side groups are common to the macromolecular structures of virtually all microorganisms which makes the organisms susceptible to the antimicrobial action of this element. Thus, silver is known as a broad spectrum antimicrobial agent.
The broad spectrum action of silver has been exploited in medical applications. Solutions of ionic silver have been used for more than 100 years for the prevention of neonate opthalmia (congenital blindness) caused by the organism responsible for gonorrhea. Ionic silver solutions have also been used for the control of bacterial infections in serious burn injuries. Although effective, it has been found that ionic silver has a very short half life or time in which it is available to attack bacteria. Tissue components including proteins and various anions in body fluids bind to silver and reduce its availability for acting on bacteria.
Another problem encountered with silver is its reaction to light. Ionic silver and salts of silver react to light energy which causes profound changes in color. An example is the photo-reduction of ionic silver, often seen as a blackening or dark staining of surfaces in contact with silver solutions. An attempt to overcome this problem of light instability was the development of the compound silver sulfadiazine (Fox, C. J., Arch. Surg., Vol. 96, p 184-188, 1968) where ionic silver was bound to sulfadiazine and delivered in an oil and water emulsion. Although this delivery vehicle of silver overcame some of the light instability issues, it still has limitations. Silver sulfadiazine, for example, is currently sold as Silvadene, (Marion Boots), its activity rapidly decays in a wound environment. The material is largely an oil-based product that stains bedding and clothing. Moreover, many patients develop allergic reactions to the sulfadiazine moiety of the product.
The control of bioburden in the wound environment has long been practiced by wound care providers. However modern wound care coverings that maintain conditions that optimize wound healing typically out last the activity of antimicrobial agents applied to the wound during dressing changes. This results in the undesirable situation where moist wound management is used to encourage tissue proliferation and repair without protection against microbial growth. Indeed the conditions that encourage tissue growth also are typically optimal conditions for microbial growth.
To overcome this limitation, manufacturers have attempted to incorporate agents into dressing materials so that there is coincident application of an antimicrobial agent along with the use of absorbent moisture management wound contact materials. Some products combine the antimicrobial, iodine, with a hydrophilic polymer for control of wound exudate and bioburden (Iodosorb and Iodoflex, Healthpoint Medical, Fort Worth Tex.). However iodine is relatively toxic at the 10,000 ppm level that is present in such products. Other wound care products utilize stabilized silver chloride in hydrophilic matrices (SilvaSorb, Medline Mundelein Il, Aquacel Ag Convatec, Skillman N.J.). Although effective in controlling bioburden, these products are useful on wounds where fluids are present so as to mobilize the silver ions. However not all wounds are sufficiently moist to enable mobilization of silver for the purpose of causing an antimicrobial effect in the wound environment. In these cases it is necessary to add the moisture. Although hydrating gels are marketed, none of them provide adequate antimicrobial protection to control the bioburden in the wound environment.
There is a need for antimicrobial wound care devices and compositions in the form of a spreadable amorphous formulation.